Educating insulin

A couple of weeks ago, I attending an annual meeting for my local JDRF chapter (my “local” chapter – the one that includes the county in which I live – happens to be farther away from home than some of the neighboring chapters, but… whatever). The featured keynote speaker was chief smart-guy-and-really-nice-guy Aaron Kowalski (official title: “Vice President of Treatment Therapies”). He’s also Type 1 and hails from New Jersey, so that’s reason enough for me to like him.

I won’t go into rehashing the bullet points of his talk. Although I did take some notes along the way for the purpose of this blog, I know that I can’t do justice in reproducing his words, delivery, and enthusiasm. That would be like me sharing my karaoke performance of “I Can’t Get No Satisfaction” – even though I don’t have the voice, can’t keep a rhythm, and haven’t got the moves like Jagger. And who wants to see an attempt at a copycat performance? So I won’t even try.

But you can see my notes by clicking here, and if you can decipher my handwriting and want me to elaborate on something, let me know. I’m certainly no journalist, but I like to write.

Aaron talked about treatments (his specialty), cure research (not his specialty, but he’s still knowledgeable), and the reason JDRF pursues both. They can be summarized in three words: LESS UNTIL NONE. Namely, until we can get rid of it entirely, let’s lessen the day-to-day burdens that living with diabetes carries, so we can devote more time to the “living” and less to the “diabetes”. Makes sense to me.

(Is it wrong to refer to Dr. Kowalski by his first name? if it is, I apologize. He just seems so down-to-Earth and approachable, that the formal approach seems unnatural).

One of the more interesting parts of his talk, and something I’ve read quite a bit about lately, is the attempt to create of Glucose Responsive Insulin, better known as “Smart Insulin”. Put simply, it’s insulin that gets stored in your body and is released when you need it.

When I first heard of this concept, I was highly pessimistic. In the mind of an electrical engineer and computer programmer, I envisioned some sort of algorithm which measures blood glucose, performs an IF…THEN comparison, and then makes a decision whether or not to allow insulin to enter the bloodstream. Kind of like an electro-mechanical closed loop system, but in the form of an injectable liquid that disappears when it’s done. Pure fantasy, I thought.

Then I learned the technique: the insulin molecules are surrounded by a shell that dissolves when it comes into contact with glucose. When enough of the shell dissolves, the insulin breaches through and escapes like a butterfly emerging from a cocoon.

I’ll bet you never heard of insulin described as a butterfly before.

One of the companies trying really hard to bring this to market is Merck, who recently acquired a smaller company that was working on the project. Apparently, it’s shown enough promise to earn additional funding from JDRF, and if it works, could make all other manufactured insulin obsolete. (Investors’ note: I currently do not own any shares of stock in Merck, though I’m passively thinking about researching this further for investment purposes. Meaning: I probably won’t, but I might. Don’t gamble your own hard-earned money in the market without the proper due dilligence.)

Meanwhile, one of the companies that is not trying to bring it to market is Lilly, as I discovered from Scott Strumello’s blog post on Monday. That could be risky for them.

Right now, insulin is – as Aaron described – the single most dangerous drug when it comes to potential adverse effects. A tiny dosage error could mean catastrophe, and yet the dosages required change all the time. Imagine: injecting a day’s worth of “smart insulin”, plus or minus a few units, and then being free to go about the day care-free. The insulin just flows around and around through the body and only activates when you need it. Automatically. No infusion sites, no continuous monitors, no triple-A batteries. Cool, huh?

Separately, JDRF is championing the cause, as revealed in this blog post earlier this month. Extracted from the final paragraph in that post, JDRF’s senior director of treat therapies, Dr. Sanjoy Dutta, states:

“Many questions still need to be answered in animal studies, and we don’t know what the regulatory pathway would be, although I do anticipate regulatory challenges. This is an uncharted pathway, and this is why JDRF is prioritizing this area of research—we can help make GRI a reality, faster.”

As I interpret this statement, JDRF will work to prepare the regulatory agencies (i.e. the FDA) while the researchers attempt to perfect the science. They’ll grease the wheels, so to speak. (My own interpretation only; I could be wrong).

Now for the part where I become skeptical — because I can’t allow myself to get caught up in the hype.

In thinking about how this “shell” around the insulin works, I can only come up with two theories: one is that the thickness of the shell dictates how much glucose is needed to free the insulin, and the other is that the composition of the shell, and not the thickness, only reacts to certain glucose concentrations.

If it’s the former, that means that the effect is cumulative, meaning extended exposure to low levels of glucose would ultimately sufficiently eat away at the shell. If it’s the latter, an overdose could be possible if the entire day’s worth of insulin gets activated all at once. There surely is an answer to this, I just don’t know what it is.

Regardless of that, it means the same vial of Smart Insulin would work the same in everybody. There would be no way to set a “target” BG as we currently do either via pumps or manual bolus calculations. YDMV would be completely disregarded.

Is that a problem? Well, during a transition onto the insulin it sure is. Many of us know, from personal experience, when the feelings of hypoglycemia set in. If our “normal” BG is in the 200 mg/dl range, we might feel low at 100. If it’s nomally 150, we might feel it at 60. Or 40. Or not at all.

If the Smart Insulin is “programmed” to activate when BG rises above 90 mg/dl (i.e. the target is 90), people starting it would feel pretty lousy until their bodies become accustomed to the new normal. That is, unless different versions of the insulin are sold, each with different targets. But I doubt that will happen.

Overall, I’m no longer the skeptic I once was. I believe this could happen. So, with this line of research, as well as others, I remain cautiously optimistic.

Maybe im wrong but i think by “regulatory pathways” he means the specific molecular interactions ( ie cell signaling, which can be though of as signal propagation that can change based on many factors) if that makes any sense… imo as cell biologist (lol) we are so fat off. At the same time research is exponentially growing in all fields so.. idlove to work on such a project – thank you scott fot the synopsis 🙂

I suppose that could be the case too. There is definitely more than one way to interpret those words. I guess I’ve been so attentive to one meaning lately that I didn’t consider any others. Thanks for the perspective.

I’m not sure if we would need two of them together — one would kind of obviate the need for the other. And while the Bionic Pancreas would be more “powerful” (with its Glucagon and sugar-raising abilities), I’d give up the cyborg-status for Glucose Responsive Insulin in a heartbeat, If it works, of course.

I’m cautiously optimistic. I don’t have enough scientific knowledge to envision how “smart” insulin would work, but I remember reading somewhere that there was a time when many scientists thought insulin could never be isolated in the first place. As for right now, I’m very thankful for the advancements that have already been made, advancements like fast-acting insulin, insulin pumps, glucose meters, and really teeny tiny sharp sharp insulin needles. They’re the next best things to functional islets of Langerhans. 😀

Reactive-style insulin isn’t too crazy — Lantus is acidic and slow-releases as the body neutralizes it’s pH.
I would imagine a main concern with smart insulin would be that there is no way to reverse the effect…it’s great at targeting high BG but now way to recover from the lows. Though I agree it is better than our current insulins. Exciting stuff!

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